Lipid remodeling plays an important role in the adaptation of plants to environmental factors, but the mechanism by which lipid remodeling mediates salt stress response remains unclear. In this study, we compared the root and leaf lipidome profiles of salt-tolerant and salt-sensitive sweet potato cultivars (Xu 22 and Xu 32, respectively) under salinity stress. After salt treatment, the leaf lipidome showed more significant remodeling than the root lipidome in both cultivars. Compared with Xu 32 leaves, Xu 22 leaves generally maintained higher abundance of phospholipids, glycolipids, sphingolipids, sterol derivatives, and diacylglycerol under salinity conditions. Interestingly, salinity stress significantly increased phosphatidylserine (PS) abundance in Xu 22 leaves by predominantly triggering the increase of PS (20:5/22:6). Furthermore, Xu 32 leaves accumulated higher triacylglycerol (TG) level than Xu 22 leaves under salinity conditions. The exogenous application of PS delayed salt-induced leaf senescence in Xu 32 by reducing salt-induced K + efflux and upregulating plasma membrane H +-ATPase activity. However, the inhibition of TG mobilization in salinized-Xu 22 leaves disturbed energy and K +/Na + homeostasis, as well as plasma membrane H +-ATPase activity. These results demonstrate alterations in the leaf lipidome of sweet potato under salinity condition, underscoring the importance of PS and TG in mediating salt-defensive responses in sweet potato leaves.